NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells

Hani Alrefai, Khalid Muhammad, Ronald Rudolf, Duong Anh Thuy Pham, Stefan Klein-Hessling, Amiya K. Patra, Andris Avots, Valesca Bukur, Ugur Sahin, Stefan Tenzer, Matthias Goebeler, Andreas Kerstan and Edgar Serfling ()
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Hani Alrefai: Institute of Pathology, Julius-Maximilians-University
Khalid Muhammad: Institute of Pathology, Julius-Maximilians-University
Ronald Rudolf: Institute of Pathology, Julius-Maximilians-University
Duong Anh Thuy Pham: Institute of Pathology, Julius-Maximilians-University
Stefan Klein-Hessling: Institute of Pathology, Julius-Maximilians-University
Amiya K. Patra: Institute of Pathology, Julius-Maximilians-University
Andris Avots: Institute of Pathology, Julius-Maximilians-University
Valesca Bukur: TRON gGmbH-Translational Oncology, Johannes-Gutenberg-University Medical Center
Ugur Sahin: TRON gGmbH-Translational Oncology, Johannes-Gutenberg-University Medical Center
Stefan Tenzer: Institute for Immunology, University Medical Center, Johannes-Gutenberg-University
Matthias Goebeler: Venereology and Allergology, University Hospital Würzburg
Andreas Kerstan: Venereology and Allergology, University Hospital Würzburg
Edgar Serfling: Institute of Pathology, Julius-Maximilians-University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.

Date: 2016
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DOI: 10.1038/ncomms11724

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